The SARS‐CoV‐2 virus Omicron variant has now supplanted wild‐type virus as the dominant circulating strain globally. Three doses of mRNA COVID‐19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron‐specific neutralization in transplant recipients after three‐doses of mRNA‐1273 vaccine. Neutralization was determined using a SARS‐CoV‐2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney‐pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA‐1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log 10 ID50 of 2.38 [range 1.34–3.57]). At 3 months, 8/51 (15.7%) were positive (median log 10 ID50 [1.68; range 1.12–3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild‐type, and Omicron vs. Delta ( p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti‐RBD response still had undetectable Omicron‐specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients.

Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target in mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of:: expression. We found that ELT-3 interacts with SKN-1 to activate transcription and that is required for enhanced expression in the mutant Furthermore, nematodes overexpressing SKN-1 required ELT-3 for life-span extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity, and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in .

SARS-CoV-2 infection has been associated with increased morbidity and mortality in organ transplant recipients, and data are limited on 2-dose or 3-dose vaccine immunogenicity against SARS-CoV-2 variants in this population. In this secondary analysis of a randomized trial of a third dose of mRNA-1273 vaccine versus placebo, the authors assessed neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses.